Despite the strong association between obesity and hypertension, little is known about the mechanism. The lack of knowledge into the pathogenesis of obesity hypertension is not surprising since few animals have been developed. Based on our previous research and the development of an animal model of obesity hypertension we postulate that obesity hypertension is primarily related to increased sodium retention by the kidney. We also speculate that this increased sodium retention is due to the combined effects of increased sympathetic nervous system activity, hyperinsulinemia and hyperaldosteronism. The following experiments will test this hypothesis: 1. The role of sodium retention on blood pressure in obesity will be assessed by measuring the change in sodium balance, plasma volume, cardiac output, regional blood flow (using radiolabeled microspheres) and blood pressure that occur in the dog with the development of obesity. 2. We speculate that weight gain will cause the dog to become "salt sensitive" (ie greater than 10% change in mean pressure will occur when the dog is switched from a low to high salt). We wxpect this "salt-sensitivity" will be associated with: both a decreased urinary sodium excretion and a negative correlation between urinary sodium excretion and the increment of change in mean pressure during a high sodium regimen; a greater loss of sodium on a low salt diet; and an increased renal blood flow, plasma aldosterone, insulin and catecholamines when the dogs become obese. 3. The role of hyperinsulinemia on blood pressure in obesity will be evaluated using a euglycemic insulin clamp. In addition, we will administer a chronic hyperinsulinemia to ten dogs. We believe that chronic hyperinsulinemia (independent of weight gain) will result in sodium retention and an increased pressure, heart rate and cardiac output. 4. The role of aldosterone will be evaluated by observing the effect of adrenalectomy on the developmemt of obesity hypertension. We expect to find that adrenalectomy will blunt but not eliminate obesity hypertension. We will also determine if increased adrenal sensitivity to angiotensin ll occurs with the development of obesity by administering graded infusions of angiotensin ll both before and after the development of obesity. 5. Finally, the role of the sympathetic nervous system will be evaluated by measuring the changes in catecholamines that occur with the development of obesity and with euglycemic hyperinsulinemia.